ES2750651T3 - Proteínas de fusión para uso en el tratamiento de acromegalia - Google Patents
Proteínas de fusión para uso en el tratamiento de acromegalia Download PDFInfo
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- ES2750651T3 ES2750651T3 ES13179177T ES13179177T ES2750651T3 ES 2750651 T3 ES2750651 T3 ES 2750651T3 ES 13179177 T ES13179177 T ES 13179177T ES 13179177 T ES13179177 T ES 13179177T ES 2750651 T3 ES2750651 T3 ES 2750651T3
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| GB201108108D0 (en) | 2011-05-16 | 2011-06-29 | Syntaxin Ltd | Therapeutic fusion proteins |
| RU2639523C2 (ru) | 2011-10-18 | 2017-12-21 | Эйлерон Терапьютикс, Инк. | Пептидомиметические макроциклы и их применение |
| JP6450191B2 (ja) | 2012-02-15 | 2019-01-09 | エイルロン セラピューティクス，インコーポレイテッド | ペプチドミメティック大環状化合物 |
| HK1205454A1 (en) | 2012-02-15 | 2015-12-18 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| US9604919B2 (en) | 2012-11-01 | 2017-03-28 | Aileron Therapeutics, Inc. | Disubstituted amino acids and methods of preparation and use thereof |
| KR20250021631A (ko) | 2014-09-15 | 2025-02-13 | 클리프톤 라이프 사이언시즈 엘엘씨 | 위장관췌장 신경내분비 신생물의 진단을 위한 조성물, 방법 및 키트 |
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| WO2016061583A1 (en) * | 2014-10-17 | 2016-04-21 | University Of Virginia Patent Foundation | Compositions and methods for treating pituitary tumors |
| EP3294318A4 (en) | 2015-03-20 | 2019-04-03 | Aileron Therapeutics, Inc. | PEPTIDOMIMETIC MACROCYCLES AND USES THEREOF |
| TW201814045A (zh) | 2016-09-16 | 2018-04-16 | 英商艾普森生物製藥有限公司 | 製造雙鏈梭狀芽孢桿菌神經毒素之方法 |
| WO2018060351A1 (en) | 2016-09-29 | 2018-04-05 | Ipsen Biopharm Limited | Hybrid neurotoxins |
| EP3312290A1 (en) | 2016-10-18 | 2018-04-25 | Ipsen Biopharm Limited | Cellular vamp cleavage assay |
| EP3375871A1 (en) * | 2017-03-13 | 2018-09-19 | SIT Biotech GmbH | Selective cell death-inducing enzyme system |
| JOP20190276A1 (ar) * | 2017-05-31 | 2019-11-27 | Napo Pharmaceuticals Inc | طرق وتركيبات لعلاج إسهال الحمض الصفراوي، والإسهال المرتبط باستئصال الأمعاء الدقيقة أو إزالة المرارة، ومتلازمة الأمعاء القصيرة |
| TWI869073B (zh) | 2018-01-29 | 2025-01-01 | 英商艾普森生物製藥有限公司 | 非神經元性ＳＮＡＲＥ裂解的肉毒桿菌神經毒素、裂解ｈＳＮＡＰ-２３之活體外方法、及經修飾ＢｏＮＴ／Ａ Ｌ鏈蛋白酶之用途 |
| GB201900621D0 (en) | 2019-01-16 | 2019-03-06 | Ipsen Biopharm Ltd | Labelled polypeptides |
| CN110801512B (zh) * | 2019-11-15 | 2023-07-18 | 中国水产科学研究院黑龙江水产研究所 | 一种用于促进哲罗鲑性腺成熟的多肽及其应用 |
| CN111388651B (zh) * | 2020-05-09 | 2022-05-03 | 山东大学齐鲁医院 | Cst-14在制备骨质疏松症治疗药物中的应用 |
| CN113257370B (zh) * | 2021-05-12 | 2022-09-02 | 中国医学科学院北京协和医院 | 基于临床病理基本信息和vista检测的pnet复发风险预测模型 |
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Family Cites Families (97)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4291022A (en) | 1975-03-11 | 1981-09-22 | Sandoz Ltd. | Organic compounds |
| US4133782A (en) | 1976-06-07 | 1979-01-09 | The Salk Institute For Biological Studies | Somatostatin analogs with dissociated biological activities |
| US4190575A (en) | 1977-12-27 | 1980-02-26 | American Home Products Corporation | Polypeptides related to somatostatin |
| EP0000053B1 (en) | 1977-06-08 | 1981-05-27 | Merck & Co. Inc. | Somatostatin analogs, process for their preparation and pharmaceutical compositions containing them |
| US4211693A (en) | 1977-09-20 | 1980-07-08 | The Salk Institute For Biological Studies | Peptides with para-substituted phenylalanine |
| LU78191A1 (de) | 1977-09-28 | 1979-05-25 | Ciba Geigy Ag | Verfahren zur herstellung von neuen cyclopeptiden |
| JPS5819669B2 (ja) | 1978-10-28 | 1983-04-19 | 白井松新薬株式会社 | 新規生理活性ペプチド化合物及びその製造法 |
| US4190648A (en) | 1979-03-13 | 1980-02-26 | Merck & Co., Inc. | Peptides having somatostatin activity |
| US4316890A (en) | 1979-03-16 | 1982-02-23 | Ciba-Geigy Corporation | Peptides and processes for the manufacture thereof |
| US4328214A (en) | 1979-07-04 | 1982-05-04 | Ciba-Geigy Corporation | Cyclopeptides and pharmaceutical preparations thereof and also processes for their manufacture |
| US4310518A (en) | 1979-10-31 | 1982-01-12 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
| US4235886A (en) | 1979-10-31 | 1980-11-25 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
| US4369179A (en) | 1979-12-14 | 1983-01-18 | Ciba-Geigy Corporation | Acylpeptides |
| US4282143A (en) | 1980-06-13 | 1981-08-04 | American Home Products Corporation | Octapeptides lowering growth hormone |
| US4360516A (en) | 1981-04-13 | 1982-11-23 | Merck & Co., Inc. | Modified D-retro cyclic hexapeptide somatostatin analogs |
| DE3264693D1 (en) | 1981-12-24 | 1985-08-14 | Ciba Geigy Ag | Cyclic octapeptides and pharmaceutical compositions thereof, and processes for their production and use |
| FR2522655B1 (fr) | 1982-03-05 | 1987-03-06 | Sanofi Sa | Analogues de la somatostatine possedant une liaison du type hydrazide et medicaments en contenant |
| US4522813A (en) | 1983-10-27 | 1985-06-11 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
| US4659693A (en) | 1984-04-30 | 1987-04-21 | Syntex (U.S.A.) Inc. | N,N'-dialkyl substituted guanidino amino acyl residue substituted GRF-analog peptides |
| US4632979A (en) | 1984-06-18 | 1986-12-30 | Tulane Educational Fund | Therapeutic LHRH analogs |
| US4684620A (en) | 1984-09-04 | 1987-08-04 | Gibson-Stephens Neuropharmaceuticals, Inc. | Cyclic polypeptides having mu-receptor specificity |
| US5003011A (en) | 1985-04-09 | 1991-03-26 | The Administrators Of The Tulane Educational Fund | Therapeutic decapeptides |
| US4650787A (en) | 1985-04-25 | 1987-03-17 | Schally Andrew Victor | Biologically active octapeptides |
| US4725577A (en) | 1985-04-25 | 1988-02-16 | Administrators Of The Tulane Educational Fund | Biologically active lysine containing octapeptides |
| US4585755A (en) | 1985-04-29 | 1986-04-29 | Merck & Co., Inc. | Cyclic and bridged cyclic somatostatin analogs useful as local anti-inflammatory agents |
| US4904642A (en) | 1985-09-12 | 1990-02-27 | The Administrators Of The Tulane Educational Fund | Therapeutic somatostatin analogs |
| US4853371A (en) | 1986-06-17 | 1989-08-01 | The Administrators Of The Tulane Educational Fund | Therapeutic somatostatin analogs |
| US4803261A (en) | 1986-06-27 | 1989-02-07 | The Administrators Of The Tulane Educational Fund | Method for synthesizing a peptide containing a non-peptide |
| HU206890B (en) | 1986-10-13 | 1993-01-28 | Sandoz Ag | Process for producing sugar-modified somatostatin peptide derivatives and pharmaceutical compositions containing them as active components |
| US4871717A (en) | 1987-01-07 | 1989-10-03 | Administrators Of The Tulane Educational Fund | Peptides |
| WO1989002897A1 (en) | 1987-09-24 | 1989-04-06 | The Administrators Of The Tulane Educational Fund | Therapeutic peptides |
| US5084555A (en) | 1989-08-21 | 1992-01-28 | The Administrators Of The Tulane Educational Fund | An octapeptide bombesin analog |
| EP0329295A1 (en) | 1988-02-01 | 1989-08-23 | The Upjohn Company | Renin inhibiting peptides with polar end groups |
| DK375789A (da) | 1988-08-18 | 1990-02-19 | Syntex Inc | Peptidderivater |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| HU208439B (en) | 1988-10-14 | 1993-10-28 | Univ Tulane | Process for producing pharmaceutical peptides |
| US5171835A (en) | 1988-10-21 | 1992-12-15 | The Administrators Of The Tulane Educational Fund | LHRH antagonists |
| CA2012115C (en) | 1989-03-15 | 2001-07-03 | Biomeasure, Inc. | Iodinated somatostatins |
| HU217636B (hu) | 1989-04-26 | 2000-03-28 | Administrators Of The Tulane Educational Fund | Szomatosztatin analógok, ezeket tartalmazó gyógyszerkészítmények és eljárás előállításukra |
| ATE140237T1 (de) | 1989-12-08 | 1996-07-15 | Univ Tulane | Oktapeptidanaloge von somatostatin mit threonin in position 6 |
| DE69112684T2 (de) | 1990-04-06 | 1996-02-01 | Univ Tulane | LHRH-Analoge. |
| AU651976B2 (en) | 1990-05-04 | 1994-08-11 | The Administrators Of The Tulane Eductional Fund | Novel synthetic GRF analogs |
| CA2081890A1 (en) | 1990-05-09 | 1991-11-10 | David H. Coy | Cyclized and linear therapeutic peptides |
| IT1240643B (it) | 1990-05-11 | 1993-12-17 | Mediolanum Farmaceutici Spa | Peptidi biologicamente attivi contenenti in catena 2-alchiltriptofano |
| IL99552A0 (en) | 1990-09-28 | 1992-08-18 | Ixsys Inc | Compositions containing procaryotic cells,a kit for the preparation of vectors useful for the coexpression of two or more dna sequences and methods for the use thereof |
| HU207104B (en) | 1991-01-25 | 1993-03-01 | Biosignal Kutato Fejlesztoe Kf | Process for producing new somatostatin analogs inhibiting tumour growth and pharmaceutical compositions comprising such compounds |
| US6083915A (en) | 1991-05-10 | 2000-07-04 | Biomeasure, Inc. | Method for treating liver cancer |
| US5240561A (en) | 1992-02-10 | 1993-08-31 | Industrial Progress, Inc. | Acid-to-alkaline papermaking process |
| WO1993015766A1 (en) | 1992-02-10 | 1993-08-19 | Seragen, Inc. | Desensitization to specific allergens |
| US5656727A (en) | 1992-09-15 | 1997-08-12 | The Administrators Of The Tulane Educational Fund | Antagonists of LHRH |
| WO1994011396A1 (en) | 1992-11-13 | 1994-05-26 | The Administrators Of The Tulane Educational Fund | Ghrh agonists |
| AU5727194A (en) | 1992-11-13 | 1994-06-08 | The Administrators Of The Tulane Eductional Fund | Ghrh agonists |
| GB9305735D0 (en) * | 1993-03-19 | 1993-05-05 | North John R | Novel agent for controlling cell activity |
| ATE399177T1 (de) | 1993-08-09 | 2008-07-15 | Sod Conseils Rech Applic | Derivate therapeutischer peptide |
| US5550212A (en) | 1993-12-17 | 1996-08-27 | The Administrators Of The Tulane Educational Fund | Analogues of hGH-RH(1-29)NH2 having antagonistic activity |
| AUPM985694A0 (en) | 1994-12-02 | 1995-01-05 | Farmer, Mostyn | Golf training aid |
| US5792747A (en) | 1995-01-24 | 1998-08-11 | The Administrators Of The Tulane Educational Fund | Highly potent agonists of growth hormone releasing hormone |
| EP0737691B1 (en) | 1995-03-13 | 1998-09-09 | Biomeasure, Inc. | Bombesin analogs |
| WO1996032126A1 (en) | 1995-04-14 | 1996-10-17 | The Administrators Of The Tulane Educational Fund | Analogs of growth hormone-releasing factor |
| GB9508204D0 (en) * | 1995-04-21 | 1995-06-07 | Speywood Lab Ltd | A novel agent able to modify peripheral afferent function |
| MY147327A (en) | 1995-06-29 | 2012-11-30 | Novartis Ag | Somatostatin peptides |
| US5942489A (en) | 1996-05-03 | 1999-08-24 | The Administrators Of The Tulane Educational Fund | HGH-RH(1-29)NH2 analogues having antagonistic activity |
| GB9617671D0 (en) | 1996-08-23 | 1996-10-02 | Microbiological Res Authority | Recombinant toxin fragments |
| WO1998008528A1 (en) | 1996-08-30 | 1998-03-05 | Biomeasure Incorporated | Method of inhibiting fibrosis with a somatostatin agonist |
| US5968903A (en) | 1998-05-07 | 1999-10-19 | Biomeasure, Incorporated | Inhibition of H. pylori proliferation |
| JP4549533B2 (ja) | 1998-05-13 | 2010-09-22 | メルツ ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト アオフ アクチェン | マスト細胞の脱顆粒を阻害するためのハイブリッドタンパク質とその使用 |
| EP1346731B1 (en) | 1998-07-22 | 2006-12-06 | Osprey Pharmaceuticals Limited | Conjugates for treating inflammatory disorders and associated tissue damage |
| MXPA01000969A (es) | 1998-07-30 | 2003-04-07 | Scient Sas Soc De Conseils De | Metodo de uso de un analogo de somatostatina. |
| GB9818548D0 (en) | 1998-08-25 | 1998-10-21 | Microbiological Res Authority | Treatment of mucas hypersecretion |
| US20040071736A1 (en) * | 1998-08-25 | 2004-04-15 | Health Protection Agency | Methods and compounds for the treatment of mucus hypersecretion |
| US6057422A (en) | 1998-11-25 | 2000-05-02 | The Administrators Of The Tulane Educational Fund | Antagonistic analogs of GH-RH inhibiting IGF-I and -II |
| US6776990B2 (en) | 1999-04-08 | 2004-08-17 | Allergan, Inc. | Methods and compositions for the treatment of pancreatitis |
| US6358697B2 (en) | 1999-04-21 | 2002-03-19 | Children's Hospital Medical Center | Intracellular pharmaceutical targeting |
| BR0011680A (pt) | 1999-06-04 | 2002-04-30 | Sod Conseils Rech Applic | Agonistas receptores de somatostatina neuromedina b, seu uso e composição farmacêutica compreendendo os mesmos |
| EP2267009B1 (en) * | 1999-08-25 | 2014-10-29 | Allergan, Inc. | Activatable recombinant neurotoxins |
| US20080032931A1 (en) * | 1999-08-25 | 2008-02-07 | Steward Lance E | Activatable clostridial toxins |
| US20030180289A1 (en) * | 1999-09-23 | 2003-09-25 | Foster Keith Alan | Inhibition of secretion from non-neuronal cells |
| GB9922554D0 (en) * | 1999-09-23 | 1999-11-24 | Microbiological Res Authority | Inhibition of secretion from non-neuronal cells |
| US7838008B2 (en) * | 1999-12-07 | 2010-11-23 | Allergan, Inc. | Methods for treating diverse cancers |
| US6831059B2 (en) * | 2000-10-20 | 2004-12-14 | Allergan, Inc. | Compositions and methods for treating gonadotrophin related illnesses |
| US6827931B1 (en) * | 2000-10-20 | 2004-12-07 | Allergan, Inc. | Method for treating endocrine disorders |
| WO2004076634A2 (en) * | 2003-02-24 | 2004-09-10 | Ira Sanders | Cell membrane translocation of regulated snare inhibitors , compositions therefor, and methods for treatment of disease |
| TW200517400A (en) * | 2003-08-05 | 2005-06-01 | Univ Tulane | Antagonistic analogs of GH-RH (2003) |
| US7514088B2 (en) * | 2005-03-15 | 2009-04-07 | Allergan, Inc. | Multivalent Clostridial toxin derivatives and methods of their use |
| CA2578911A1 (en) * | 2004-09-01 | 2006-03-09 | Allergan, Inc. | Degradable clostridial toxins |
| US8399400B2 (en) * | 2004-12-01 | 2013-03-19 | Syntaxin, Ltd. | Fusion proteins |
| EP1830872B1 (en) * | 2004-12-01 | 2010-11-17 | Health Protection Agency | Fusion proteins |
| GB0426394D0 (en) * | 2004-12-01 | 2005-01-05 | Health Prot Agency | Fusion proteins |
| GB0426397D0 (en) * | 2004-12-01 | 2005-01-05 | Health Prot Agency | Fusion proteins |
| JP2008535486A (ja) * | 2005-03-15 | 2008-09-04 | アラーガン、インコーポレイテッド | クロストリジウム毒素標的細胞に対する改変された標的能力を有する修飾クロストリジウム毒素 |
| ES2341892T5 (es) | 2005-09-19 | 2019-03-27 | Allergan Inc | Toxina clostridial activable por toxinas clostridiales |
| EP1834962A1 (de) | 2006-03-15 | 2007-09-19 | Biotecon Therapeutics GmbH | PEGyliertes mutiertes Clostridium botulinum Toxin |
| US7993656B2 (en) * | 2006-07-11 | 2011-08-09 | Allergan, Inc. | Modified clostridial toxins with enhanced translocation capabilities and altered targeting activity for clostridial toxin target cells |
| WO2008008805A2 (en) | 2006-07-11 | 2008-01-17 | Allergan, Inc. | Modified clostridial toxins with enhanced translocation capabilities and altered targeting activity for non-clostridial toxin target cells |
| BRPI0915142A8 (pt) * | 2008-06-12 | 2018-01-02 | Syntaxin Ltd | Polipeptídeos, ácido nucleico e usos dos mesmos |
| WO2009150469A2 (en) * | 2008-06-12 | 2009-12-17 | Syntaxin Limited | Suppression of neuroendocrine diseases |
| US10057187B1 (en) | 2015-05-27 | 2018-08-21 | Amazon Technologies, Inc. | Dynamic resource creation to connect client resources in a distributed system |
-
2009
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- 2009-06-11 EP EP09762018.1A patent/EP2310028B1/en active Active
- 2009-06-11 KR KR1020117000251A patent/KR101642363B1/ko not_active Expired - Fee Related
- 2009-06-11 CA CA2727082A patent/CA2727082C/en not_active Expired - Fee Related
- 2009-06-11 ES ES13179177T patent/ES2750651T3/es active Active
- 2009-06-11 EP EP13179177.4A patent/EP2719392B1/en active Active
- 2009-06-11 US US12/996,643 patent/US20110171191A1/en not_active Abandoned
- 2009-06-11 ES ES09762018.1T patent/ES2614990T3/es active Active
- 2009-06-11 JP JP2011513056A patent/JP5728380B2/ja active Active
- 2009-06-11 CN CN201410295607.7A patent/CN104328100B/zh not_active Expired - Fee Related
- 2009-06-11 BR BRC10915888A patent/BRPI0915888E2/pt not_active IP Right Cessation
- 2009-06-11 EP EP19175007.4A patent/EP3590956A1/en active Pending
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2010
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2009150469A2 (en) | 2009-12-17 |
| AU2009259033B2 (en) | 2013-11-07 |
| ES2614990T3 (es) | 2017-06-02 |
| EP2310028B1 (en) | 2016-11-16 |
| ZA201008536B (en) | 2012-05-30 |
| JP5891258B2 (ja) | 2016-03-22 |
| IL209855A (en) | 2013-09-30 |
| KR20110038017A (ko) | 2011-04-13 |
| KR101642363B1 (ko) | 2016-07-25 |
| CN102112145B (zh) | 2014-07-30 |
| EP2310028A2 (en) | 2011-04-20 |
| BRPI0915888A2 (pt) | 2020-06-30 |
| EP3590956A1 (en) | 2020-01-08 |
| CN104328100A (zh) | 2015-02-04 |
| AU2009259033A1 (en) | 2009-12-17 |
| BRPI0915888E2 (pt) | 2020-09-01 |
| US20110171191A1 (en) | 2011-07-14 |
| WO2009150469A3 (en) | 2010-07-15 |
| JP5728380B2 (ja) | 2015-06-03 |
| CN102112145A (zh) | 2011-06-29 |
| CA2727082A1 (en) | 2009-12-17 |
| EP2719392A1 (en) | 2014-04-16 |
| EP2719392B1 (en) | 2019-07-24 |
| JP2014195454A (ja) | 2014-10-16 |
| CA2727082C (en) | 2019-02-26 |
| IL209855A0 (en) | 2011-02-28 |
| JP2011522560A (ja) | 2011-08-04 |
| CN104328100B (zh) | 2019-08-23 |
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